The release of apoptotic molecules from mitochondria is activated by the pro-apoptotic Bcl-2 proteins in programmed cell death. We first ask whether the pro-apoptotic Bcl-2 proteins activate mitochondria in long-term depression (LTD). We will alter the expression of pro-apoptotic Bcl-2 proteins in hippocampal neurons, then examine -amino-3-hydroxy-5-methylisoxazole-4- propionic acid (AMPA) receptor endocytosis and LTD in these neurons. To investigate how casapses mediate AMPA receptor endocytosis, we will use antibodies against caspase-3 to immunoprecipitate proteins that bind to caspase-3 in LTD. We have made a construct to overexpress caspase-3 in hippocampal neurons and are performing the immunoprecipitation experiment.